We propose to test the efficacy and safety of daily nitroglycerin for reduction in risk of fractures in a year randomized trial (Nitric Oxide Fracture Trial - aka 'NO Fracture Trial'). Our primary aim for the trial is to test the hypothesis that dail nitrates, compared with alendronate 70 mg once weekly reduces the risk of nonvertebral fracture in women at high risk for such fractures. The secondary aims are to test the hypotheses that, compared with alendronate, daily nitrate administration: (a) Is not inferior to alendronate fr reduction in risk of vertebral fracture; (b) reduces the risk of clinical fractures; and (c) producs greater increases in bone mineral density (BMD) at femoral neck and lumbar spine. Lastly, we will compare the risk of adverse events between nitroglycerin and alendronate. The goal in the planning phase is to develop an NIH proposal for funding for the NO Fracture Trial. The specific aims for the planning phase are: (1) decide the formulation and dose of the nitrate treatment; (2) finalize the sample size and enrollment criteria, and plan recruitment strategies; (3) identify and engage clinical sites capable of on-time recruitment of enough participants; (4) complete the study protocol, operations manuals, data collection forms and plans for data management; (5) develop the plan for safety and data monitoring and a data safety monitoring board; (6) obtain the necessary regulatory approvals for the trial; (7) develop the study budget and strategies to minimize the cost of the trial; and (8) write and submit the proposal for the NO Fracture Trial. This planning phase will lead to a well-reasoned design, efficient and feasible plan and proposal for the NO Fracture trial. We expect the NO Fracture Trial to demonstrate that the use of daily nitrate safely reduces the risk of nonvertebral fractures more than alendronate. If successful, findings from this trial would lead to world-wide use of this inexpensive medicine with greater reduction in the personal and social burden of fractures than achievable with current therapy.